Towards a world free of Thalassemia

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Thalassemia is a genetic blood related disorder due to absent or reduced production of hemoglobin, a protein responsible for carrying oxygen to the tissues.

Each red blood cell may contain between 240 and 300 million molecules of hemoglobin.

A hemoglobin molecule has two sub-units commonly referred to as alpha and beta.

Both sub-units are necessary to bind oxygen and deliver it to cells and tissues in the body.

The alpha globin gene cluster controls the production of alpha chains, and similarly the beta globin gene cluster produces beta chains.

A lack of a particular subunit determines the type of the resulting thalassemia (alpha or beta).

Thalassemia is derived from the Greek word 'thalassa' meaning 'the sea' because the condition was first described in populations living near the Mediterranean Sea.

However, it is now very well known that thalassemia is the most common inherited single-gene disorder in the world with the highest prevalence in areas where malaria was or still is endemic (Mediterranean Basin, Australasia, the Americas and Africa).

In many parts of the world, thalassemia still represents a major public health concern.

In beta-thalassemia, the clinical presentation occurs from six to 24 months of age.

The severity of the damage depends on the type of the gene mutation.

Some mutations (beta-zero) prevent any formation of beta chains; others (beta-plus) allow some beta chain formation to occur.

In the severe form of the disease, the bone marrow expands as it attempts to keep pace with the perceived need for new red blood cells, setting the stage for moderate-to-severe skeletal deformities and pain.

If left untreated, affected infants fail to thrive and become progressively pale.

Feeding problems, diarrhea, irritability, recurrent bouts of fever, leg ulcers, osteoporosis, thrombotic complications, and progressive distention of the abdomen caused by liver and spleen enlargement may occur.

Risk Factors

People with Mediterranean (including North African), Middle Eastern, or Southeast Asian ancestry are at higher risk of being carriers of beta-thalassemia than are other populations.

Beta-thalassemia is a recessively inherited genetic disorder that, in most cases, requires two defective beta-globin genes to trigger the disease.

If only one mutant copy of the beta-globin gene is inherited, no symptoms may appear; this condition is called beta-thalassemia minor or beta-thalassemia trait. Hence, a positive family history of beta-thalassemia is an important indication for an individual to seek consultation as he/she might be at high risk of carrying the disease.

Diagnosis and Management

Diagnosis of thalassemia can be made as early as 9-11 weeks in pregnancy using procedures such chorionic villi sampling. Amniocentesis (analyzing the amniotic fluid) may be carried out at 16-20 weeks of pregnancy. Individuals can also be tested for thalassemia through routine blood counts.

Early treatment of beta-thalassemia has proved to be very effective in improving the quality of life of patients.

Long term transfusion support is the backbone of conservative management in beta-thalassemia patients to alleviate anemia.

Frequent blood transfusions usually lead to iron overload that is countered by iron chelation therapy to prevent damage to the internal organs.

In recent years, bone marrow transplantation has shown promise in many patients with beta-thalassemia where a successful transplant can eliminate the patients' dependency on blood transfusions.

Treatment of beta-thalassemia major is currently an expensive option and has great financial implications for any health authority where the disease has a high prevalence.

The baseline results for the total lifetime treatment costs for a patient with beta-thalassemia (up to 60 years of age) are estimated to be $416,000; thus, an average of about $7000 annually.

Untreated beta thalassemia eventually leads to death usually by heart failure; therefore genetic testing, counseling, and prenatal diagnosis are very important in the prevention, management and treatment of this disease.

In some endemic regions, such as Mediterranean countries, long-established control programs have achieved 80-100% prevention of newly affected births.

World Epidemiology of Thalassemia

Thalassemia was originally thought to be a disease limited to the Mediterranean region, however it is now known that it occurs widely throughout many parts of the world.

Thalassemia has been identified across southern Europe from Portugal to Spain, Italy and Greece, as well as in a number of central European countries and parts of the former Soviet Union.

Thalassemia also affects the Middle East through to Iran, Pakistan, India, Bangladesh, Thailand, Malaysia, Indonesia and southern China, as well as countries along the north coast of Africa and in South America.

Population migration and intermarriage between different ethnic groups has introduced thalassemia in almost every country of the world, including northern Europe where thalassemia did not previously exist and where now it is becoming a major public health problem.

While reliable sources estimate that about 1.5% of the global population -- 80 million- 90 million people -- are carriers of beta-thalassemia, with about 60,000 affected children born annually, the great majority in the developing world, it is certain that coming updated figures will demonstrate that those are gross underestimates.

There is still little accurate data available on carrier rates (gene frequencies) in many population groups, particularly in areas of the world known or expected to be heavily affected.

According to the records of the Thalassemia International Federation, however, only about 200,000 patients with thalassemia major are alive and registered as receiving treatment around the world.

Beta-thalassemia is endemic in almost all countries of the Arab world probably due to the historical presence of malaria in the region, and the high level of consanguinity.

Carrier frequencies of beta-thalassemia vary from 1% to 5%.

The molecular basis of beta-thalassemia has been extensively studied in various Arab countries. A total of more than 60 mutations in the beta-globin gene have been reported in patients with beta-thalassemia in the Arab world.

A recent genetic study in Dubai demonstrated the presence of 50 mutations in the UAE population. As expected, each Arab country, Mediterranean or Asian, has its own characteristic spectrum of mutations.

While some mutations appear in most countries, others seem to be regionally restricted paving the way to studies on their historical origins.